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Chemogenetic stimulation of a retinal circuit activates brain noradrenergic neurons, prevents apoptosis and suppresses depression-like behaviors

Authors :
Hannah E. Bowrey
Mohammdkhani A
Gary Aston-Jones
Mohsen Omrani
Morgan H. James
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

A chronically dysregulated locus coeruleus (LC) system gives rise to mood disorders. In particular, prolonged LC hyperactivity often underlies stress disorders, whereas chronically reduced function often underlies symptoms of depression. Owing to its location deep in the brainstem, LC is difficult to access which limits translational approaches that involve manipulating these neurons. Here, we circumvent this problem by utilizing the retina as a chemogenetic target for commandeering a multsynaptic circuit to LC. We show that activation of this pathway can prevent depression-like behavior and associated pathology of the LC-noradrenergic (NA) system caused by light deprivation. Additionally, we show that melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are the likely cell type responsible for initiating activity in this pathway. By capitalizing on this ocular route of designer receptor delivery, we demonstrate a novel, minimally-invasive method for manipulating this deep-brain circuit that is relevant to a wide array of neuropsychiatric disorders.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........97a94f8cdc83b0713efbe0ebdac3ef64
Full Text :
https://doi.org/10.1101/2021.04.20.440684